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Genetic counseling: Angelman Syndrome-2
Angelman Syndrome Introduction *Introduce myself *What are the major concerns that you would like to have addressed today? *Who referred you to genetics? *Outline session **obtain medical history and family history **Dr. Saal will come in and do physical exam **discuss condition and testing options **address specific concerns Medical History *complete intake **seizures? **medications? **sleeping patterns? **communications skills? **hyperactivity? **developmental assessment? **services received? **unusual behaviors? laughter? generally happy? **problems with balance? walking? **MRI? *complete pedigree Incidence *1/12,000-1/20,000 Clinical Features *Feature present in about 100% of patients **normal prenatal and birth history ***normal birth weight and head circumference ***no major birth defects **normal metabolic and hematologic profile **structurally normal brain on MRI ***mild cortical atrophy or dysmyelination possible **delayed motor development ***apparent by 6-12months ***usually severe **speech impairment ***usually < 1 or 2 words ***receptive language better than expressive language **movement and balance disorder ***abnormal gait ***tremulous movements of limbs **Unusual behaviors ***Frequent laughter and smiling/happy demeanor ***Excitability ***Hyperactivity ***Short attention span *Features Present in more than 80% of patients *Microcephaly **caused by delayed head growth **present by age 2 *Seizures **Beginning by age 3 *Abnormal EEG **Characteristic large amplitude slow-spike waves *Features found in 20-80% of patients **Strabismus **Hypopigmentation of skin and eyes **Feeding problems in infancy **Wide mouth, wide spaced teeth **Increased sensitivity to heat **Sleep disturbances Management *Behavioral modification for undesirable/socially unacceptable behaviors *Medication for seizures *Generally do not receive medication for hyperactivity *Occupation therapy for fine motor control *Speech therapy focusing on nonverbal means of communication *Safe, confining bedroom for nighttime sleeplessness *Monitoring for onset of scoliosis Genetics *Caused by loss of maternal contribution of region 15q11-q13 **65-75% of patients have 3-5Mb interstitial deletion **3-7% of patients have paternal uniparental disomy **2-6% of patients have imprinting defect **5-11% of patients have mutations in the UBE3A gene within this region **11-20% of patients have another unknown cause Molecular Testing *DNA methylation analysis **78% of patients with a deletion, uniparental disomy, or an imprinting defect are detected this way **further testing is required to distinguish between these types ***FISH analysis can detect deletions (70% of patients) ***DNA polymorphism testing can detect uniparental disomy ***Patients with imprinting defects have 15q11-q13 polymorphisms from both parents ****imprinting center defect characterization available on research basis only *UBE3A mutation analysis **11% of patients with Angelman syndrome have identifiable mutations Recurrence Risks *Families Genetic Mechanism Risk to Siblings **65-75% 3-5Mb deletion <1% **<1% unbalanced translocation as high as 50% *small interstitial deletion **3-7% paternal uniparental disomy <1% **<1% uniparental disomy with approaching 100% Robertsonian translocation **1-3% imprinting defect as high as 50% (if deletion in imprinting center mother has deletion) **1-3% imprinting defect likely <1% without deletion **11% UBE3A mutation as high as 50% if mother has deletion **10-15% other unidentifiable cause most cases not familial (but could be as high as 50%) Psychosocial Issues *Who is involved in care of patient? *What is the living situation? *How will having a diagnosis change care and management? *How will having a diagnosis affect you? *Are there concerns about recurrence risks? References *Geneclinics: Angelman syndrome *Smith's Recognizable Patterns of Human Malformations *Clinical Genetics Lecture Notes The information in this outline was last updated in 2002. Material obtained under GFDL Licence from http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling